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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Gastric cancer,immunohistochemistry,microsatellite instability,microsatellite analysis
- چکیده:
- چکیده انگلیسی: Introduction: Microsatellite instability (MSI) is a hallmark of defective DNA mismatch repair (MMR) of genes
especially MLH1 and MSH2. It is frequently involved in the carcinogenesis of various tumours including gastric
cancer (GC). However, MSI in GCs have not been reported in Malaysia before. Objective: This study was conducted
to determine the microsatellite instability (MSI) status in gastric cancer by microsatellite analysis, sequencing, its
association with MLH1 and MSH2 protein expression and H.pylori infection by immunohistochemistry. Method:
A total of 60 gastric cancer cases were retrieved. DNA was extracted from paired normal and tumour tissues while
MLH1 and MSH2 protein expression as well as H. pylori status were determined by IHC staining. For microsatellite
analysis, polymerase chain reaction (PCR) was performed for paired tissue samples using a panel of five microsatellite
markers. MSI-positive results were subjected for DNA sequencing to assess mutations in the MLH1 and MSH2 genes.
Results: Microsatellite analysis identified ten MSI positive cases (16.7%), out of which only six cases (10.3%) showed
absence of MLH1 (n=3) or MSH2 (n=3) protein expression by IHC. The most frequent microsatellite marker in MSI
positive cases was BAT26 (90%). Nine of ten MSI positive cases were intestinal type with one diffuse and all were
located distally. H. pylori infection was detected in 13 of 60 cases (21.7%) including in three MSI positive cases. All
these results however were not statistically significant. Our sequencing data displayed novel mutations. However these
data were not statistically correlated with expression levels of MLH1 and MSH2 proteins by IHC. This may be due
to small sample size to detect small or moderately sized effects. Conclusion: The frequency of MSI in this study was
comparable with published results. Determination of affected MMR genes by more than two antibodies may increase
the sensitivity of IHC to that of MSI analysis.- انتشار مقاله: 12-03-1397
- نویسندگان: Nor Hasyimah Haron,Ezanee Azlina Mohamad Hanif,Mohd Rizal Abdul Manaf,Jasmi Ali Yaakub,Roslan Harun,Ramelah Mohamed,Isa Mohamed Rose
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Relapse,triple negative breast cancers,TNBCs,epigenetic modifiers,FEC
- چکیده:
- چکیده انگلیسی: Breast cancer treatments leads to variable responses. Hormonal therapy is beneficial to receptor positive breast cancer
subtypes and display better clinical outcome than triple negative breast cancers (TNBCs) with FEC (5-Fluorouracil,
Epirubicin and Cyclophosphamide) the mainstay chemotherapy regiment. Owning to their negative expressions of
estrogen (ER), progesterone (PR) and HER2 receptors, disease recurrence and metastasis befalls some patients indicating
resistance to FEC. Involvement of epigenetic silencing through DNA methylation, histone methylation, acetylation and
sumoylation may be the key player in FEC chemoresistance. Epigenetic and molecular profiling successfully classified
breast cancer subtypes, indicating potential driver mechanisms to the progression of TNBCs but functional mechanisms
behind chemoresistance of these molecular markers are not well defined. Several epigenetic inhibitors and drugs have
been used in the management of cancers but these attempts are mainly beneficial in hematopoietic cancers and not
specifically favourable in solid tumours. Hypothetically, upon administration of epigenetic drugs, recovery of tumour
suppressor genes is expected. However, high tendency of switching on global metastatic genes is predicted. Polycomb
repressive complex (PRC) such as EZH2, SETD1A, DNMT, is known to have repressive effects in gene regulation and
shown to inhibit cell proliferation and invasion in breast cancers. Individual epigenetic regulators may be an option
to improve chemo-drug delivery in cancers. This review discussed on molecular signatures of various breast cancer
subtypes and on-going attempts in understanding underlying molecular mechanisms of epigenetic regulators as well
as providing insights on possible ways to utilize epigenetic enzymes/inhibitors with responses to chemotherapeutic
drugs to re-program cellular and biological outcome in TNBCs.- انتشار مقاله: 26-02-1397
- نویسندگان: Ezanee Azlina Mohamad Hanif,Shamsul Azhar Shah
- مشاهده